New Control System of the Body Discovered – Important Modulator of Immune Cell Entry into the Brain – Perhaps New Target for the Therapy

Researchers in Berlin, Germany have ameliorated inflammation of the brain in mice caused by immune cells. A receptor they discovered on the surface of T cells in the central nervous system (CNS) plays the key role. The researchers showed that this bradykinin receptor 1 (B1) controls the infiltration of immune cells into the CNS. When they activated B1 in mice with encephalitis, they were able to slow down the crossing of the immune cells through the blood-brain-barrier into the CNS. As a result, the inflammation markedly decreased. The work by Dr. Ulf Schulze-Topphoff, Prof. Orhan Aktas, and Professor Frauke Zipp (Cecilie Vogt-Clinic, Charité – Universitätsmedizin Berlin, Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and NeuroCure Research Center) together with researchers in Canada and the USA may unveil a new target for the treatment of chronic inflammatory diseases such as multiple sclerosis (MS) (Nature Medicine, doi 10.1038/nm.1980)*.

It has been known for a long time that T cells can attack
the body’s own structures and, if they infiltrate the CNS, cause diseases such
as multiple sclerosis (MS). The T cells damage the myelin sheath, the material
that surrounds and protects the fibers of nerve cells. This damage slows down
or blocks messages between the brain and the body, leading to various symptoms
of MS such as impaired movements.

The molecular analysis of damaged tissue from patients with
MS led the researchers to the B1-receptor. The data they evaluated showed that
two different pathways known to play a crucial role in the cardiovascular area
also seem to play an important role in the CNS: namely, the
renin-angiotensin-system, and the kallikrein-kinin-system, the latter of which
the researchers in Berlin put their focus on.

The B1-receptor is part of the kallikrein-kinin-system.
Together with Professor Alexandre Prat from the Université de Montréal,
Montréal, Canada, and Professor Lawrence Steinman from Stanford University in
Stanford, California, USA, the researchers in Berlin detected the B1-receptor
on T cells of MS patients as well as on T cells of mice with encephalitis, an
inflammation of the brain.

The disease got worse in those mice that lacked B1 on their
T cells. Therefore, using a certain substance (Sar-[D-Phe]desArg9-bradykinin),
they activated the receptor in mice which had B1 on their T cells. As a result,
the entry of T cells into the CNS slowed down and the clinical symptoms of the
inflammation markedly decreased.

“We have discovered a control mechanism, which reduces
inflammation caused by the immune system” neurologist and MDC research group
leader Professor Zipp explains. “It remains to be seen if we succeed in
developing a new therapy for chronic inflammation in the CNS, such as MS, in the
future.”